RT Journal Article SR Electronic T1 Inhibition of P-TEFb by DRB Suppresses SIRT1/CK2α Pathway and Enhances Radiosensitivity of Human Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6981 OP 6989 VO 34 IS 12 A1 ZHI-QIANG WANG A1 CASEY L. JOHNSON A1 AMIT KUMAR A1 DAVID P. MOLKENTINE A1 JESSICA M. MOLKENTINE A1 TATIANA RABIN A1 KATHRYN A. MASON A1 LUKA MILAS A1 UMA RAJU YR 2014 UL http://ar.iiarjournals.org/content/34/12/6981.abstract AB Background: Positive transcription elongation factor-b (P-TEFb) is a complex containing CDK9 and a cyclin (T1, T2 or K). The effect of inhibition of P-TEFb by 5,6-dichloro-l-β-D-ribofuranosyl benzimidazole (DRB) on cell radiosensitivity and the underlying mechanisms were investigated. Materials and Methods: Six human cancer cell lines were subjected to 3H-uridine incorporation, cell viability and clonogenic cell survival assays; cell-cycle redistribution and apoptosis assay; western blots and nuclear 53BP1 foci analysis after exposing the cells to DRB with/without γ-radiation. Results: DRB suppressed colony formation and enhanced radiosensitivity of all cell lines. DRB caused a further increase in radiation-induced apoptosis and cell-cycle redistribution depending on p53 status. DRB prolonged the presence of radiation-induced nuclear p53 binding protein-1 (53BP1) foci and suppressed the expression of sirtuin-1 (SIRT1) and casein kinase 2-alpha (CK2α), suggesting an inhibition of DNA repair processes. Conclusion: Our findings indicate that DRB has the potential to increase the efficacy of radiotherapy and warrants further investigation using in vivo tumor models.